DESCRIPTION (Adapted from the applicant's abstract and specific aims): The proposed work represents a continuation of the investigation of the roles that copper plays in embryonic and fetal development. The Specific Aims are: 1) to characterize the morphological and histological changes associated with copper deficiency-induced structural defects during embryonic and fetal periods in the rat; 2) to characterize the influence of copper deficiency on the extent of ECM cross-linking and vascular integrity and, the role of oxidant stress in abnormal embryonic development; 3) to determine metabolic decisions regarding the "trafficking" and prioritization of copper in the embryo when copper is limiting; and, 4) to define the extent to which cardiac and cranial defects persist following correction of copper deficiency. The primary focus is early embryonic development. The investigators have developed an embryo culture system which duplicates defects that are observed in embryos in association with in vivo maternal copper deficiency allowing the study of mechanisms important to regulating normal and abnormal embryologic development.